Asymmetric synthesis of 3-substituted unsaturated prolines from chiral sulfoximine substituted allyl titanium(IV) complexes

An asymmetric synthesis of the 3-substituted Δ^3,4-unsaturated prolines 7a-e and 3-substituted 4-methylene prolines 14a-c starting from the corresponding γ,δ-unsaturated α-amino acids 4a-e and 11a-c, respectively, is described. Amino acid derivatives 4a-e and 11a-d were obtained through aminoalkylation of the corresponding sulfoximine substituted allyl titanium(IV) complexes 2a-e and 10a-d, respectively, with the N-tert-butylsulfonyl imino ester 3. Activation of sulfoximines 4a-e and 11a-c through methylation of the sulfoximine group followed by a KF mediated isomerization of the vinyl aminosulfoxonium salts 5a-e and 12a-c, respectively, to the corresponding allyl aminosulfoxonium salt 6a-e and 13a-c, respectively, and a subsequent intramolecular nucleophilic substitution of the allylic aminosulfoxonium group afforded the enantio- and diastereomerically pure proline derivatives in medium to high yields.